The proposed research seeks to identify those factors which are responsible for increases in the susceptibility of photoreceptor cells to degeneration. The susceptibility of photoreceptor cells varies as a function of age and (topographical) location in the retina. Experiments are designed to test the hypothesis that changes in structural and chemical properties of the photoreceptor cells underlie the variation in their susceptibility to degeneration. Photoreceptor-specific degeneration will be produced by exposing the retina of rats to constant light. Using morphometric and electroretinographic techniques, the severity of light-induced degeneration will be determined as a function of age and retinal region. Several other parameters, such as rod outer segment length, disk packing density, renewal rate, lipid to opsin ratio and rhodopsin concentration will be examined in non-exposed animals, also as a function of age and retinal region, to evaluate their role in influencing photoreceptor susceptibility to degeneration. A new approach to testing the hypothesis of interest will utilize isolated rat and frog retinas maintained in vitro for extended electroretinogram recording. Retinas will be incubated in supplemented media containing various levels of nutrients thought to protect against photoreceptor cell degeneration. Electroretinogram deterioration caused by incubation with ferrous ion will be monitored and retinas subsequently will be examined by microscopy. In this manner, the capability of supplemented nutrients in altering the susceptibility of photoreceptor cells to degeneration will be assessed. The proposed experiments should help to elucidate the basis for changes in both the susceptibility of photoreceptor cells to degeneration and their protective capability. This information could be helpful in efforts to devise preventative measures against retinal degenerations of similar mechanism in humans.